Abstract Background: Lipid metabolism depends on Lipoprotein lipase enzyme whose variants were reported associated with type 2 diabetes mellitus (T2DM) and obesity. The lipoprotein lipase (LPL) gene was linked to lipoprotein metabolism, while its pathogenic genetic variants were linked to obesity, insulin resistance (IR) and so diabetes. Aim of Study: To study the association between LPL (rs1801177, rs320) variants and diabetes regarding disease incidence and susceptibility to obesity. Patients and Methods: This case control study included 280 subjects, T2DM (n=140) compared to healthy control subjects (n=140). Lipoprotein lipase variants (rs1801177, rs320) across the lipoprotein lipase gene were genotyped by real-time PCR using the TaqMan allele discrimination assay. Results: The studied variant genotypes frequency was significantly different between diabetic and non diabetic subjects, p-value=0.008 & 0.034 for rs1801177, rs320, re-spectively. A significant association was detected between LPL gene rs1801177 & rs320 variants and BMI, waist circumference and HbA1C, FBG, TG & HDLc. There's a positive correlation between BMI and LPL rs 1801 177 variant (r=0.367, p=0.001), There's a moderate positive correlation between waist circumference and LPL rs1801177 variant (r=0.383, p=0.001), positive correlation with FBG (r=0.342, p=0.001), positive correlation with HbA1c (r=0.405, p<0.001) and a moderate positive correlation between TG level and LPL rs1801177 variant (r=0.464, p=0.025). A weak negative correlation between HDL level and LPL rs320 variant (r=–0.225, p=0.007). Conclusions: Both variants were significantly associated with parameters related to obesity and T2DM (BMI, waist circumference, FBG, HbA1c, TG & HDLc). Due to the poly-genic nature and the high prevalence of obesity & T2DM, further studies with larger study population are needed to assess our results.