Context: Solanum xanthocarpum Schrad and Wendl (Kaṇṭakāri) is a diffuse herb with prickly stem, traditionally used for the treatment of inflammation and one in the group of daśamūla (group of ten herbs) herbs commonly used drug in Ayurveda. Aims: In continuation of search for potent natural anti-inflammatory agents, the present research work was planned to evaluate the anti-inflammatory activity of ethanol extract of S. xanthocarpum whole plant. Settings and Design: The ethanol extract was evaluated at dose 10, 30 and 100 mg/kg p.o. in rats. Materials and Methods: Using pharmacological screening models carrageenan induced rat paw edema, histamine induced rat paw edema and cotton pellet granuloma in rats. Statistical Analysis Used: Data obtained was analyzed statistically using analysis of variance followed by post-hoc Dunnett test, P < 0.05 is considered as statistically significant. Results: Acute treatment didn′t show anti-inflammatory activity against carrageenan and histamine induced paw edema. However, administration of 100 mg/kg p.o for 7 day reduced the granuloma formation in cotton pellet granuloma model. Conclusions: Present results support the traditional use of plant for anti-inflammatory activity. In brief, the results provide scientific pharmacological basis for the therapeutic use of S. xanthocarpum.