Objective: In current study, influence of environmental situation and genetic variations on renal clearance and urinary excretion of roxithromycin was determined in local healthy adult female subjects. Roxithromycin is a secondgeneration macrolide widely used in human clinics for different infectious diseases. Methods: For experimentation, ten healthy adult female were selected. Roxithromycin 300 mg (Rulide®) was given to each volunteer. Blank samples each for urine and blood was collected prior administration of roxithromycin and after that blood samples were collected at 1,2, 4 and 6 hours and urine samples were collected at 1, 2, 4, 6, 8, 10, 12, 24 and 48 hours post medication. Blood samples were centrifuged to separate plasma. A high performance liquid chromatography (HPLC) method was used to find out the concentration of drug in urine and plasma samples. In plasma and urine concentration of drug and endogenous creatinine were used to calculate renal clearance and urinary excretion of drug. Results: In present study the renal clearance of roxithromycin was 0.08 ± 0.01 ml/min/kg. Mean ± SE value for clearance ratio between drug clearance and creatinine clearance was 0.04 ± 0.00 which indicates reabsorption (back diffusion) of roxithromycin. The cumulative percentage of oral dose of 300 mg tablet of roxithromycin excreted through urine during 48 hours was 12.87 ± 1.31 percent. Conclusion: Renal clearance and urinary excretion observed in present study variates from previous studies conducted in other geographical regions under different environmental conditions. Variations in present study may be due to genetic variations. It is concluded from the study that renal clearance and urinary excretion study is required under indigenous conditions.