Vitamin D deficiency and vitamin D receptor (VDR) gene polymorphisms have been linked to T2DM and diabetic nephropathy, this study aimed to evaluate vitamin D deficiency and VDR gene polymorphisms ApaI (rs7975232), FokI (rs2228570) in Egyptian patients with T2DM and detect the associations of these polymorphisms with the pathogenesis of diabetic nephropathy. About 75 patients with end-stage renal diseases (ESRD), 75 patients with T2DM disease, 75 patients with diabetic nephropathy, and thirty normal controls were enrolled. Biochemical analysis included; 25 hydroxy vitamin D [25(OH)D], FBS, PPS, HOMA-IR, fasting insulin, HBA1c, blood urea, serum creatinine, eGFR, Albumin-creatinine ratio, total calcium, phosphorus, and lipid profile. VDR gene polymorphisms were detected by PCR- RFLP technique. This current study showed the lower mean levels of vitamin D in patient with T2DM (31.9 ± 8.1) ng/ml and (10.8 ±8.1) ng/ml in diabetic nephropathy in comparison to control subjects (44.9 ±20.7) ng/ml, P< 0.001. Vitamin D insufficiency was more prevalent in T2DM and diabetic nephropathy. There was a significant increase in (ff), (AA) genotypes and (f), (A) alleles frequencies in T2DM group. We concluded from our study that vitamin D deficiency was highly prevalent in our Egyptian patients with T2DM and diabetic nephropathy. There were statistically significant differences between patients with T2DM and controls in FokI genotype and alleles distribution, which could be a risk factor for Egyptian patients with T2DM. Whoever, there was a protection effect of (a) allele of ApaI genotype in Egyptian patients.