The purpose of this study was to observe the effect of an alcoholic extract of Cicer microphyllum (I(3) M/38/A001) (whole plant without seeds and flowers) on the immunological parameters of sheep red blood cell immunized normal and chronically stressed Swiss albino mice. Estimation of T-cell subsets (CD3(+) , CD4(+) /CD8(+) ), CD80/CD86, CD28, CD 69, costimulatory molecules and Th1/Th2 cytokines was carried out using a flow cytometer. This was followed by study of the delayed type hypersensitivity response, in-vitro lymphocyte proliferation assay and measurement of Th1/Th2 cytokines in isolated peripheral blood mononuclear cells by flow cytometry. An enzyme immune assay was used to analyse corticosterone levels in the serum of chronically stressed animals. We found that oral administration of I(3) M/38/A001 once daily at the graded doses of 6.25, 12.5, 25, 50, 100 and 200 mg/kg p.o. enhanced the proliferation and differentiation of T lymphocytes in sheep red blood cell normal and chronically stressed mice, as shown by flow cytometric analysis. The extract selectively induced type 1 immunity: it guided enhanced expression of Th1 cytokines, interferon-γ and interleukin-2, while no significant change in interleukin-4 (Th2 cytokine) levels was observed. Confirmation of Th1 polarization was confirmed by the augmented levels of interferon-γ and interleukin-2 in isolated peripheral blood mononuclear cells. A significant suppression of raised corticosterone levels was also observed in stressed animals, which suggests the extract's normalizing effect on the hypothalamic-pituitary-adrenal axis. Co-stimulatory molecules, CD28, CD69, CD80 and CD86, which are important secondary signals for the activation of the immune system, elicited significant expression in I(3) M/38/A001 treated mice. Our studies show the immune potentiating and immune recuperative effect of the test drug in sheep red blood cell-immunized normal and chronically stressed mice. © 2010 The Authors. JPP © 2010 Royal Pharmaceutical Society.