Doxorubicin (DOXO) is a potent chemotherapeutic used mainly against solid tumours; however, it has several side effects that can limit its clinical use. On the other hand, the effect of DOXO upon lymphocyte function is controversial. Some studies demonstrate that DOXO administration in vitro suppresses T-cell activation, while the cellular function has been shown to increase in vitro. The objective of this study was to investigate the effect of DOXO on lymphocyte cytokine production in rats. The animals were divided into: SAL (control, n=10) and DOX (DOXO treated, n=10). The DOX group received only one DOXO dose at 15kgKg^-1 by intraperitoneal injection. Forty-eight hours after DOXO administration, the animals were killed by decapitation. IL-2 production was significantly enhanced (p<0.05) in lymphocytes from rats treated with DOXO (169.17±21.73 pgmL10⁵ cell) as compared to cells from SAL (45.92±10.53pgmL10⁵ cell). The administration of DOXO decreased (<0.05) IL-4 production in the DOXO group (29.85±13.09pgmL10⁵cell) relative to the SAL group (75.08±15.31pgmL10⁵cell). The IL-2/IL-4 ratio was higher (<0.05) in the DOX group (5.99±0.44), as compared to SAL group (0.73±0.12). In conclusion, our results suggest that a dose of DOXO promotes an alteration in the Th1/Th2 balance, promoting a shift towards a Th1-dominant cytokine response.