Upon reading The Kingdom and People of Siam by Sir John Bowring in 1857, Mouhot decided to travel to Indochina to conduct a series of botanical expeditions for the collection of new zoological specimens.

On his first expedition, he visited Ayutthaya, the former capital of Siam (already charted territory), and gathered an extensive collection of insects, as well as terrestrial and river shells, and sent them on to England.

In his posthumously published Travels in Siam, Cambodia and Laos, Mouhot compared Angkor to the pyramids, for it was popular in the West at that time to ascribe the origin of all civilization to the Middle East.

"Mouhot also wrote that: "At Ongcor, there are ...ruins of such grandeur... that, at the first view, one is filled with profound admiration, and cannot but ask what has become of this powerful race, so civilized, so enlightened, the authors of these gigantic works?

Mouhot himself, however, did not seem to be a hardcore colonialist, for he occasionally doubted the beneficial effects of European colonisation: "Will the present movement of the nations of Europe towards the East result in good by introducing into these lands the blessings of our civilization?

"However, Mouhot appears in his notes as genuinely interested in South East Asia and its culture, and kept in mind the benefits he thought France could provide to those countries.

[3] Page 175: "People are astonished to see insignificant production and no industry in these regions that are so fertile and so rich, but they are generally unaware that the kings and mandarins enrich themselves through despoilment and corruption, through all the abuses that ruin work and halt progress.

Let this country be administered with wisdom and prudence, with loyalty and protection for the people, and everything will change with marvellous rapidity.”[3] Mouhot also highlighted he saw France already provided Cambodia, at his time: (page 179) "Had it not been for the war that France has been waging against the Empire of Annam for the past two years, it is probable that today the last hour would have sounded for the little kingdom of Cambodia, whose destiny, with little doubt, is to die out and be assimilated into the neighbouring peoples.”[3] Mouhot died of a malarial fever on his fourth expedition, in the jungles of Laos.

In 1867 the French commander Ernest Doudart de Lagrée of the Mekong_expedition_of_1866–1868, following an order from the Governor of Cochinchina, built a small monument near where they believed Mouhot's grave would have been.

De Lagrée gave this eulogy: "We found everywhere the memory of our compatriot who, by the uprightness of his character and his natural benevolence, had acquired the regard and the affection of the natives.

"Sixteen years later when the French explorer Dr Paul Neis travelled up the Nam Khan river he found only "a few bricks scattered on the ground".

During the years of the Second Indochina War Mouhot's tomb was consumed by the jungle and lost until it was rediscovered in 1989 by French scholar, Jean-Michel Strobino, together with Mongkhol Sasorith, a Lao historian.