Aims: The most common use of Citrullus colocynthis is to treat diabetes and decrease blood glucose in Iranian traditional medicine. Due to the effects of fructose on increasing glucose and creating insulin resistant (IR) models, this study aimed to compare the effect of different parts of Citrullus colocynthis extract on insulin resistant of male rats.

Methods: In this experimental study, 63 adult male Wistar rats were used. After making IR with fructose 10% induced in drinking water for 8 weeks, the animals were divided into 7 (control, sham, aqueous and hydro-alcoholic extracts of crust and seed and hydro-alcoholic extracts of pulp) groups. After separation of serums, glucose, insulin and insulin resistance index were measured. The results were statistically analyzed by ANOVA and post hoc LSD tests.

Results: Hydro-alcoholic extract of crust increased glucose in comparison with control group (p<0.05). Glucose level was decreased in aqueous extract of seed group in comparison with sham group (p<0.05). Weight was increased in aqueous extract of seed group in comparison with control (p<0.01) and sham (p<0.05) groups. Hydro-alcoholic extract of crust leads to decreasing insulin in comparison with sham group (p<0.05). In Hydro-alcoholic extract of seed’s group, insulin level was increased compared with control group (p<0.01). Insulin level was increased in aqueous extract of seed group in comparison with control (p<0.001) and sham (p<0.05) groups.

Conclusion: The most effective part of Citrullus colocynthis in treatment of diabetes type II is seed and the most harmful part is crust.