Aim: to assess the relation between plasma level of osteopontin and matrix metalloproteinase-2 and the severity and progression of diabetes mellitus. METHODS: measurement of plasma osteopontin, and matrix metalloproteinase-2 using enzyme linked immunosorbent assay(ELIZA) in 75 adult patients suffering from type 2 diabetes(divided into 3 subgroups: uncomplicated D.M, diabetic nephropathy and diabetic retinopathy). Results: plasma level of osteopontin was significantly increased in uncomplicated D.M group, diabetic nephropathy group and diabetic retinopathy group (P =0.001) and there was non significant positive correlation between osteopontin and all the tested parameters in all groups but, high significant positive correlation with urinary albumin in diabetic nephropathy group (P=0.005) and significant positive correlation in diabetic retinopathy group (P=0.025)as compared to control subjects. Serum level of MM-2 was significantly increased in uncomplicated D.M group and diabetic retinopathy group but significantly decreased in diabetic nephropathy group (P =0.001), there was non significant positive correlation between MMP-2 and all the tested parameters in all groups but, high significant positive correlation with BMI in uncomplicated D.M, (P=0.004) and significant positive correlation with BMI in diabetic retinopathy group (P=0.016) as compared to control subjects. Conclusion: these results indicating that plasma level of OPN and MM-2 was increased with the severity of D.M, plasma level of OPN increased with the progression of diabetic nephropathy and that OPN may be useful as a biomarker to trace progression of diabetic nephropathy. Also, These results indicating that MM-2 may contribute to the pathogenesis of diabetic nephropathy and diabetic retinopathy.