Calotropis gigantea (Linn.) R.Br. (Asclepiadaceae), commonly known as milkweed or swallow- wort, is found chiefly in wasteland throughout India. It has been reported as a traditional folkloric medicine in treatment of asthma in the Indian literature. Roots containing α-and β-amyrin are reported to possess anti-lipoxygenase activity. Hence, our objective was to evaluate the effect of the methanolic extract of Calotropis gigantea (CG) root on egg albumin induced passive paw anaphylaxis and compound 48/80 induced mast cell degranulation in rats. CG were given at doses of 100, 200, 400 mg/kg, p.o., to rats. We found that CG significantly increases percentage inhibition of paw edema volume at all doses but shows significant percentage protection of the mast cells at 400 mg/kg. p.o., to rats. Hence, the present investigation confirm the use of CG as anti-anaphylactic and mast cell stabilizing in treatment of asthma.