Background: It is known that patients with high insulin resistance (IR) have a slower rate of decline in the viral load of HCV RNA compared to patients with low IR. Objective: to evaluate relation between insulin resistance on sustained treatment response with direct oral antiviral drugs on relapsed Egyptian chronic HCV patients. Patients and Methods: 50 patients with chronic hepatitis C met inclusion criteria divided into Group I were non responders to treatment and achieved sustained virological response (SVR) at week 12 on retreatment and Group II were non responders to treatment and failed to attain SVR after 12 weeks of retreatment. All participants received the direct antiviral therapy (DAA) sofosbuvir and daclatasvir for 12 weeks. HOMA-IR was calculated and PCR was done before treatment, at end of treatment, 12 weeks and 3 months after end of treatment. Results: there was a highly significant correlation between HOMA-IR and liver enzymes, lipid (P<0.01) and significant relation between HOMA-IR and BMI and waist circumference. After 6 months of treatment there was highly significant increase in insulin sensitivity and decrease in insulin resistance in patients after eradication of HCV (P<0.01). 12 cases of insulin resistance pretreatment and after 6 months: 3 cases HCV -ve became non-insulin resistant, 2 cases HCV -ve became insulin resistant, 2 cases of HCV -ve developed DM and 5 cases had no changes (still insulin resistant).   Conclusion: prevalence of insulin resistance and diabetes mellitus in patients with chronic hepatitis C was due to multiple causes and clearance of HCV infection improves insulin resistance; not directly related to DAA.