Senna italica Mill. belonging to the family Fabaceae has been used traditionally to treat various ailments diseases including skin diseases, fever, jaundice, stomachache, burns and inflammation. The aim of the present study was to evaluate the phytochemical profile and the anti-inflammatory activity of the methanol leaf extract of the plant. Preliminary phytochemical screening and oral acute toxicity studies were carried out using standard protocols. Anti-inflammatory activity was investigated in Wistar rats using cotton pellet-induced granuloma model at doses of 250, 500 and 1000 mg/kg. Hematological and biochemical parameters were also evaluated. Phytochemical screening revealed the presence of tannins, saponins, carbohydrate, alkaloids, flavonoids, and steroids. The oral median lethal dose was estimated to be greater than 5000 mg/kg. The extract reduced wet granuloma weight with percentage inhibition of 5.9%, 52.9% and 47.1 % at doses of 250, 500 and 1000 mg/kg respectively compared to the negative control. At same doses, the extract showed 14.3%, 17.1% and 28.6% inhibition in weight of dry cotton pellet. A significant (p<0.05) reduction was observed in platelets, platelet lymphocyte ratio, creatinine, aspartate aminotransferase and alkaline phosphatase levels.The result from this study suggests that the methanol leaf extract of Senna italica has anti-inflammatory activity supporting the traditional use of the plant in the treatment of inflammation and inflammatory related diseases.