From 1614 on, he waged a five-decade long struggle against the Safavid Iranian domination of Georgia in the course of which he lost several members of his family and ended his life as the Shah's prisoner at Astarabad at the age of 74.

Kakheti, the easternmost Georgian polity that emerged after the fragmentation of the Kingdom of Georgia in the late 15th century, was within the sphere of influence of the Safavid dynasty of Iran.

Until the early years of the 17th century, the kings of Kakheti had maintained peaceful relations with their Iranian suzerains, but their independent foreign policy and diplomacy with the Tsardom of Russia had long irked the shahs of Iran.

[6] Since the new monarch was still underage, Queen Ketevan temporarily assumed the function of a regent and arranged, in 1606, Teimuraz's marriage to Ana, daughter of Mamia II Gurieli, Prince of Guria on Georgia's Black Sea coast.

Teimuraz, threatened with an Iranian invasion, attempted to buy peace by sending his two sons, Alexander and Leon, and his mother Ketevan as honorary hostages to the shah's court in 1613.

This time he was aided by the Georgian nobleman, Giorgi Saakadze, an able fighter who had formerly enjoyed much influence in the service of Luarsab II of Kartli until a threat to his life had led him to defect to the shah.

[7] Teimuraz continued to seek and exploit Russian and Ottoman aid against Iran and remained a rallying point for opposition to the Safavids, encouraging his subjects to reject a Muslim replacement for him.

[6] Meanwhile, Abbas I's appointed governor of Kakheti, Paykar Khan, embarked on a campaign to resettle the depopulated areas of eastern Georgia with Turkic nomads, sparking a rebellion by the remaining Georgian population.

Later in 1626, the rivalry among the Georgian leaders culminated in the battle at Lake Bazaleti in which the royal army won a decisive victory, driving Saakadze into exile to Constantinople where he was put to death in 1629 after serving a brief military career under Sultan Ibrahim I.

Determined to eliminate the Safavid hegemony over Georgia, Teimuraz sent his ambassador, Niciphores Irbachi, to Western Europe and requested the aid from Philip IV of Spain and Pope Urban VIII.

However, the rulers of Europe were too involved in the Thirty Years' War (1618–1648) to be concerned about the fate of a small Caucasian kingdom, and nothing came of this mission, the publication of the first Georgian printed book Dittionario giorgiano e italiano ("Georgian-Italian Dictionary"; Rome, 1629) by Stefano Paolini and Niciphores Irbachi being the only result of this embassy.

In 1641, Teimuraz, who was intent upon uniting all of eastern Georgia under his rule, backed a nobles' conspiracy against Rostom, which finally ruined his relations with the ruler of Kartli.

In order to end resistance in Kakheti once and for all, Shah Abbas II revived a plan to populate the country with the Turkic nomads, a measure that incited a general uprising in 1659.

Vakhtang V sent Teimuraz to Isfahan and the old Georgian ex-monarch was honorably received by Abbas II, but cast into prison when his grandson Heraclius returned from Russia and made a failed attempt at taking control of Kakheti.

During his first creative period, 1629–34, when he was relatively secure on his throne, Teimuraz translated and adapted from Persian the romances of Layla and Majnun (Georgian: ლეილმაჯნუნიანი, Leilmajnuniani), Yusuf and Zulaikha (იოსებზილიხანიანი, Iosebzilikhaniani), The Rose and the Nightingale (ვარდბულბულიანი, Vardbulbuliani), and The Candle and the Moth (შამიფარვანიანი, Shamiparvaniani).

[11] The second period, 1649–56, was in exile at the court of his brother-in-law, Alexander III of Imereti, when Teimuraz, in his own words, used poetry as therapy: "Tears flowed mercilessly like the Nile from my eyes.

In his poems, Teimuraz laments the destruction of his kingdom, condemning the "transient and perfidious world", and mourns the fate of his family and friends, cursing the cause of his own and his people's misfortunes, the "bloodthirsty king of Persia.

The poem, which in the words of Professor Donald Rayfield proves that "whatever Georgia lost in the king, it gained in the poet", is influenced by the medieval Georgian hagiographic genre, vividly describing the tortures to which the queen mother is subjected after she refuses to follow Shah Abbas's order to renounce Christianity.