Aims: Diabetes is one of the metabolic diseases. According to side effects of medication and high costs of treatments, medical plants are of attention. This study was done to compare the anti-diabetic effect of Citrullus colocynthis fruit powder with metformin on blood glucose level. Materials & Methods: 32 mature male rats with an average weight of 250-300gr were divided into four groups a negative control (normal diet), a positive control (distilled water), a sham (14 mg/kg metformin) and a treatment (50mg/kg Citrullus colocynthis). Type 2 diabetes induced by intraperitoneal injection of 60mg/kg of Streptozotocin (two times, with 48h interval) in all except the negative control group. These solutions regularly administrated by using oral gavage for 6 weeks. After 12 hours of fasting, before the first and after the last doses, the blood glucose was measured via the tail vein. Statistical analysis was performed in SPSS 18 software by one way ANOVA with repeated measurement tests. Findings: The decreasing level of glucose between metformin and Citrullus colocynthis groups was significant in day 28 (p<0.05), But it was not significant in day 42. Conclusion: Metformin can be replaced by Citrullus colocynthis in reducing blood glucose.