Background: Cannabinoid receptor-1 (CNR1) gene polymorphism is reportedly associated with diabetic nephropathy (DN) in patients with type 2 diabetes mellitus (T2DM). It has been confirmed that CNR1 plays an important role in the peripheral organs, including the kidneys. Alterations of cannabinoid receptor expression and activity have been discovered in various renal diseases such as diabetic nephropathy. The goal is to find out if the CNR1 genetic variations rs750464422 T/C and rs1776965150 T/A affect how likely T2DM Iraqi patients are to get DN. Methods: In this cross-sectional study, we included 100 patients who have had T2DM. We classified the participants into two groups: the first group was comprised of 50 patients with DN (the case group), and the second group was comprised of 50 patients without DN (the control group). CNR1 rs rs750464422, and rs1776965150 polymorphisms were genotyped in DN patients and controls by polymerase chain reaction (PCR). Results: Data analysis revealed that there was a significant difference in the frequencies of the TC genotypes of CNR1 rs750464422 between patients with DN and controls (p=0.001), while there were non-significant differences in the distribution of CC genotypes (p=0.6). Moreover, the C allele of this polymorphism was associated with an increased risk of DN compared to the T allele (p=0.001, OR=3.29 and 95% CI= 1.58-7.07). We predicted that patients with the rs1776965150 genetic polymorphism have a significant difference in the TA genotype (p=0.05, OR= 0.95, and 95% CI= 0.1-1.10), while the A allele frequency shows a non-significant difference (p=0.2). Conclusion: CNR1 genetic variations, rs750464422 polymorphisms, were correlated with the development of DN, while rs1776965150 polymorphisms were not associated with DN