Cissampelos sympodialis (Cs) is an herb used for the treatment of several diseases due to its anti-inflammatory properties. The present study investigated the effect of oral administration of Cs extract on STZ-induced diabetes in mice. Diabetes was induced by three i.p. injections of STZ (100 mg/Kg) in male BALB/c mice. The mice were randomly divided into four groups: control group, STZ group, Cs 0.4 group (0,4mg/Kg) and Cs 4 group (4mg/Kg). At the 50th day of protocol mice were euthanized and serum insulin and fasting blood glucose were determined by ELISA and electrical feeder, respectively. Changes in pancreas architecture were assessed through histopathological examination using hematoxilin-eosin method. We also evaluated cytokine (IL-10, IL-4, and IL17) production in spleen cell culture from diabetic mice stimulated or not with pokeweed mitogen by ELISA. The treatment with Cs extract was not able to reduce blood glucose levels or to increase insulin production in any of the time points evaluated after STZ injection. However, treatment with Cs extract was able to prevent damage on islets’ morphology. Additionally, Cs extract at the concentrations evaluated was not able to modulate cytokine production in vitro by spleen cells. issampelos sympodialis can indirectly contribute to the reduction of the inflammatory response characteristic on STZ-induced diabetes in mice, which might be associated to the reduction of the damage on the islets.