Aim of the study: We investigated the effects of Sphaeranthus indicus on mast cell stabilizing activity to provide scientific basis for the clinical use of S. indicus. Materials and methods: The protective effect of different extracts of whole plant of S. indicus against compound 48/80 and sheep serum induced mast cell degranulation was evaluated. Results: Ethanol extract of S. indicus at the doses of 150 mg/kg and 300 mg/kg and ethyl acetate extract at the dose of 100 mg/kg, 150 mg/kg and 300 mg/kg showed slightly better protection of mast cell degranulation (77-86%) than the standard drug ketotifen (75%) in the sheep serum model. These extracts also showed better mast cell stabilizing activity (77-88%) than the standard drug (69%) when peritoneal mast cells are treated with compound 48/80. Conclusion: These results suggest that S. indicus has potent mast cell stabilizing effects thereby inhibiting mediator release from mast cells. © 2009 Elsevier Ireland Ltd. All rights reserved.