The objective of the present study was to evaluate the in-vitro and in-vivo anti-inflammatory activity of aqueous and ethanolic leaf extract of the Kalanchoe pinnata plant. Aqueous and ethanolic extract of the leaves was prepared by cold maceration. The anti-inflammatory activities of the aqueous and ethanolic extracts of the leaves were performed by both in vitro and in vivo methods. The in vitro method was estimated by the human red blood cell membrane stabilization (HRBC) method and the in vivo method was estimated on the carrageenan-induced paw edema. Data were analyzed by one-way analysis of variance (ANOVA) and Dunnett’s t-test was used as the test of significance. P-value <0.05 was considered as the minimum level of significance. The data revealed that varying concentrations of aqueous and ethanolic Kalanchoe pinnata plant significantly stabilized erythrocyte membrane against hypotonicity-induced hemolysis in a dose-dependent manner. Similarly, the plant extracts showed significant anti-inflammatory activity in dose dose-dependent manner in the carrageenan-induced paw edema model. The inhibition of paw edema was found to be 86.38% for diclofenac 10mg/kg, 67.91% for ethanolic extract (300mg/kg), 71.52% for ethanolic extract (600mg/kg), 68.61% for aqueous extract (300mg/kg) and 83.75% for aqueous extract 600mg/kg maximally. Among the extracts, aqueous extract showed more inhibitory activity on inflammation. The results of the present study demonstrate that aqueous and ethanolic leaf extract of kalanchoe pinnata possesses significant (P < 0.05) anti-inflammatory activity.