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We investigated the effects of acetylsalicylic acid (ASA) on the total myenteric neuronal population in the descending colon in Trypanosoma cruzi-infected mice. Thirty-five male Swiss mice, 60 days old, were divided into a control group (C group), control group treated with ASA (CA group), infected group (I group), and infected group treated with ASA (IA group). A total of 1300 trypomastigotes of the Y strain of T. cruzi were intraperitoneally inoculated in the IA and I groups. The CA and IA groups were treated with ASA intraperitoneally. At 75 days post-infection (dpi), all of the animals were sacrificed. Neurons in the colon were stained with Giemsa, quantified, and measured. No difference in the course of infection was observed between the IA and I groups, reflected by the parasitemia curve. Acetylsalicylic acid treatment in the CA and IA groups did not alter the total number of myenteric neurons compared with the C and I groups. The CA and IA groups exhibited an increase in the nuclear area, cytoplasmic area, and neuronal body area compared with the C and I groups. Future studies should elucidate the mechanism of action of ASA against Chagas' disease in the chronic phase.