The effect of a methanolic extract of Cardiospermum halicacabum L was studied against cyclophosphamide(CTX)-induced toxicity in mice. Administration of CTX (25 mg/kg b.wt, i.p.) for 10 days produced significantmyelosuppression as evidenced by a decreased WBC count and bone marrow cellularity. Co-treatment withCardiospermum significantly increased the total WBC count, bone marrow cellularity and α-esterase positivecells, and the relative organ weights of spleen as well as thymus compared to the CTX alone treated group.Cardiospermum further reduced the enhanced levels of ALP, GPT, LPO, and proinflammatory cytokine TNF-α,and also significantly increased the glutathione (GSH) level in CTX treated animals. The lowered levels ofother cytokines like IFN-γ, IL-2, GM-CSF, after CTX treatment were also found to be increased by extractadministration. Histopathological analysis of small intestine also suggested reduction of CTX-induced intestinaldamage. Moreover the extract down-regulated the inducible nitric oxide synthase (iNOS) and cyclo-oxygenase-2(COX-2) mRNA expression in LPS stimulated macrophages. These studies indicate that C. halicacabum couldreduce cyclophosphamide induced oxidative stress and immunosupression through enhancing the antioxidantstatus and immunomodulation by stem cell proliferation.