Background <p>Diabetic nephropathy (DN) exists as a serious renal condition brought on by destruction to the kidney’s glomerular blood capillaries. Glomerular and tubular damage biomarkers may predict early renal failure and structural abnormalities before microalbuminuria appears. The&#xa0;aim of this study is evaluating the role of long noncoding RNAs (LncRNAs) MALAT1 and CASC2 expressions in predicting DN in cases with type 2 diabetes. This was a case-control study, including 90 subjects allocated into three groups: 30 apparently healthy subjects as control group, 30 diabetic patients without DN and 30 patients with DN. LncRNAs MALAT1 and CASC2 expression were assessed by quantitative real time PCR.</p> Results <p>LncRNA MALAT1 expression was elevated in cases who had diabetic nephropathy when compared to both diabetic patients without nephropathy and controls and in diabetic patients without nephropathy when compared to healthy controls. LncRNA CASC2 expression was significantly lower in diabetic nephropathy patients compared to both diabetic patients without nephropathy and controls. MALAT1 expression displayed a significant positive correlation with HbA1c, creatinine, urinary β2MG, and albumin creatinine ratio (ACR). While a significant negative correlation between MALAT1 and eGFR was revealed. There was a significant negative correlation between CASC2 and MALAT1, creatinine, ACR, HbA1c as well as urinary β2MG. A statistically significant positive correlation between CASC2 and eGFR was detected. MALAT1 and CASC2 had 83.3%, 90% sensitivity and 80%, 86.7% specificity in predicting DN. Combining both markers demonstrated better performance in predicting diabetic nephropathy.</p> Conclusions <p>LncRNA MALAT1 expression is upregulated and LncRNA CASC2 expression is downregulated in patients with diabetic nephropathy. They can act as independent predictors for nephropathy in diabetic patients.</p>