Background: Systemic lupus erythematosus is a chronic inflammatory disease that can affect any organ, but very often injures the kidney. It is more prevalent in women than men across all age groups and populations; the femaleto-male ratio is higher at reproductive age, ranging between 8:1 and 15:1, and is lowest in prepubertal children at about 4:3. Aim of the Work: To study the effect of intravenous cyclophosphamide versus oral mycophenolate (MMF) in the treatment of lupus nephritis (LN). Subjects and Methods: This was a prospective, randomized, comparative study on the efficacy of I.V cyclophosphamide compared to oral MMF in the induction therapy of LN. In this study 40 patients of systemic lupus erythematosus with lupus nephritis, were included. All patients were divided randomly into two groups. The first group included 20 female patients who given Oral Corticosteroid 1mg /kg and intravenous cyclophosphamide 500mg once every two weeks for 6 months. The second group included 20 patients receiving oral corticosteroid 1mg /kg and oral mycophenolate 2-3g/day (1200 mg/m2) for 6 months. Results: - As regard serum creatinine, alb/cr ratio, serum albumin, ESR, Anti DNA, c3, and eGFR there was a highly significant difference between before/after the treatment in each group, with no significant difference comparing the two group to each other. Conclusion: In our study, both MMF and IVC show significant improvement in patients with lupus nephritis with no superiority of one of them to the other.