This study examined the effects of quercetin and apigenin on the changes in the production of antibodies and cytokines as well as lymphocyte proliferation in aflatoxin $B_1$ ($AFB_1$)-treated mice. Serum titers of immunoglobulin (Ig) subsets, such as IgA, IgG1, and IgG2a, were changed significantly by the $AFB_1$ treatment. These changes were inhibited by supplementation with flavonoids. $AFB_1$ exposure also suppressed the secretion of cytokines, such as interferon-$gamma$, interleukin-4, and tumor necrosis factor-$alpha$, in splenocytes in response to lipopolysaccharide or concanavalin A. A co-treatment with apigenin suppressed more sensitively the $AFB_1$-mediated alteration of cytokine secretion and DNA synthesis by splenocytes than quercetin. This study suggests that flavonoids have preventive effects against $AFB_1$-mediated immunotoxicity. In particular, apigenin is more capable of chemopreventing such toxicity than quercetin.