Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance and abnormalities in insulin production. Apelin is associated with insulin resistance. According to the anti-diabetic properties of curcumin, the purpose of this study was to compare the effects of curcumin and nano-curcumin intake on insulin resistance and serum levels of fasting blood sugar (FBS), Apelin, and lipid profile (cholesterol, triglyceride, LDL, HDL and VLDL) in T2DM rats. Forty-eight male Wistar rats were divided into six groups: Control, diabetic, diabetic treated with two doses of curcumin (100 and 200 mg/kg) and diabetic treated with two doses of nano-curcumin (100 and 200 mg/kg). Induction of T2DM was performed by intraperitoneal injection of Nicotinamide (110 mg/kg) and Streptozotocin (45 mg/kg) in the fasting state. Rats received different doses of nano-curcumin and curcumin by gavage (daily) for 28 days. At the end of the intervention period, insulin resistance and serum levels of FBS, apelin and lipid profiles were measured. Insulin resistance and serum levels of FBS, Apelin, cholesterol, triglycerides, LDL, and VLDL were significantly decreased in diabetic rats treated with curcumin and nano-curcumin (p<0.05) so that nano-curcumin in reducing lipid profile is more effective than curcumin (P<0.05). Serum level of HDL in nano-curcumin groups was significantly higher than diabetic and curcumin groups (p<0.05). Also, with increasing insulin resistance, serum level of apelin increased (P<0.05). The therapeutic effects of curcumin and nano-curcumin were effective in decreasing insulin resistance, serum levels of FBS, apelin and lipid profile. The dose of 100 mg/kg nano-curcumin was more effective in reducing lipid profile. © 2020 Shamsi-Goushki et al.