Ageratum conyzoides Linn is a medicinal plant used for diverse ethnomedicinal applications including anti-ulcer treatment. Usually, protection of gastric mucosa from injury or ulceration is dependent on the efficacy of intrinsic or induced protective factors against erosive effects of aggressive factors. In this study, our aim was to ascertain the gastroprotective activity of methanolic leaf extracts of A. conyzoides L. and assess the associated roles of gastric mucous cells and p53 protein. This study involved 25 adult male Wistar rats divided into five groups (A-E). Groups A and E were used as normal and test controls while B-D were administered with extracts at 100, 300 and 500 mg/kg body weight for 28 days. Gastric mucosal injury was induced via pyloric ligation method. Gastric tissues were processed, stained with periodic acid-Schiff and immunostained for p53 protein (using monoclonal antibody). Stained sections were quantified using image-J software, data obtained were statistically analyzed. The results showed significant increase (p<0.05) in mucous cell population but no significant increase in p53 protein expression in gastric tissues of treated animals. This implied that increase in mucous cell count and down-regulation of p53 protein in gastric tissues play key role in gastroprotective activity of methanolic extracts of A. conyzoides L. Key words: Ageratum conyzoides, mucous cell, p53 protein, gastroprotection, rats.