He is best known for creating comic strips that lampooned lifestyles in Filipino youths including Plain Folks and Tisoy, the latter which was adapted into two films and a television series as a screenwriter.
His main character, Tisoy (slang for "mestizo"), and cast members such as Aling Otik, Maribubut, Caligula, Tatang, Tikyo and Kinse, soon became established in Philippine pop culture.
The strip humorously depicted the socio-political woes of ordinary Filipinos, as represented by the tailless Everymouse hero, Ikabod - who became as iconic in his own way as that other popular cartoon rodent, Mickey Mouse.
Marcelo often used the strip to caricature political figures from Ferdinand Marcos and Corazon Aquino to Joseph Estrada and Gloria Macapagal Arroyo, re-imagining them as mice.
He was collaborated again with Imee to participate the project adapted from Ferdinand's novel into an 54-minute adult animated film titled Tadhana (1978), which originally conceived as a television pilot due to a lengthy process.
[14] He was featured in Time for its cover story Mighty Pens, published on September 12, 1988, for his bold commentaries on the current socio-political state of the country through his comic strips, making him the only Asian cartoonist.
[7] Marcelo was appointed the title of Senior Lecturer in Film Animation at the UP College of Fine Arts by a chairwoman of Department of Visual Communication, Margarita Revilla Simpliciano, during the deanship of National Artist Napoleon V.
In 1998, Marcelo received the Cultural Center of the Philippines' Centennial Artist Award, the only cartoonist to be honored; cited him by CCP for excellence in the visual arts and for helping define national identity by taking a stand on political and social issues.