Momordica grosvenori (MG), a traditional medicinal herb in China used as a substitute sugar for obese and diabetic patients, exhibited an enhancement of immunity. Heme oxygenase-1 (HO-1) is among the acute phase proteins that play an important role in the inflammatory process and have antiinflammatory activities with their antioxidant properties. The hypothesis that MG could modulate an imbalance of the cellular immune system and prevent the progression of diabetes mellitus, via induction of HO-1 protein expression was investigated. Diabetes was induced in male Balb/c mice by intraperitoneal injection of alloxan (200 mg/kg). The mice were randomly assigned to non-diabetic and diabetic groups, and further subdivided according to their treatments: control (distilled water), low dose MG (150 mg/kg) and high dose MG (300 mg/kg), which were administered by gavage in 24 h cycles over a 30 day period. MG administration effectively regulated the immune imbalance in diabetic mice, principally by upregulating the CD4(+) T lymphocyte subsets, and remodeling the intracellular cytokine profiles (reducing the expression of pro-inflammatory Th1 cytokines towards a beneficial Th2 pattern), ascribed to its induction and upregulation of HO-1. In conclusion, MG exhibited antidiabetic effects and may be used as a new natural drug for the treatment of diabetes.