Contrast-induced nephropathy (CIN) is a common condition associated with serious adverse outcomes. It may be preventable because its risk factors are well characterized and the timing of renal insult is commonly known in advance.The optimal strategy to prevent contrast nephropathy has not been established.  The AIM of this study is to compare the efficacy of short-term infusion regimens of sodium bicarbonate, theophylline and the combination of both for prevention of contrast-induced nephropathy in rats. METHODS: This work was conducted on seventy adult male albino rats. They were classified into seven groups. Group I: control group; Group II: received 1 mL intravenous bicarbonate (8.4%); Group III: received 15 mL/kg intra-peritoneal theophylline; Group IV:  received 6mL/kg intravenous urografin; Group V: intravenous bicarbonate three hours before urografin; Group VI: intra-peritoneal theophylline one hour before urografin; Group VII: bicarbonate three hours and theophylline one hour before urografin injection. Baseline blood samples were collected and analyzed for biochemical parameters then after waiting 48 hours for the development of contrast nephropathythe rats were sacrificed and biochemical parameters were re-examined:serum creatinine, blood urea nitrogen (BUN), creatinine clearance andfractional excretion of sodium (FENa⁺). Light microscopic examination for the kidneys sections was done. RESULTS: after 48 hours water deprivation, highly significant decrease in mean body weight was found in all groups when compared with the baseline mean values.On comparing baseline with the after experiment parameters mean values within each group, there was significant increase in the mean values of serum creatinine and BUN and significant decrease in the creatinine clearance and fractional excretion of sodium percentage in groups group IV, group V and group VI; while, group VII showed insignificant difference between baseline and after experiment in all the studied parameters. Comparing after experiment parameters between group IV and control group showed a highly significant increase in the mean values of serum creatinine, BUN and significant decrease in the creatinine clearance and fractional excretion of sodium percentage. Furthermore, group V and group VI showed marked amelioration of all after experimental parameters but it still shows significant difference when compared with the control group. Group VII showed insignificant difference in all parameters when compared with the control group. Histopathological examination of the examined specimens from group IV showed severe damage consisting of tubular necrosis and protein cast, tubule dilatation, intra-tubular obstruction by protein casts. The examined kidney specimens from group V and group VI showed mild damage while the percentage of pathological changes were significantly decreased when compared with group IV. Sections from group VII showed marked improvement of all changes. CONCLUSION: urografin injection resulted in marked nephrotoxicity manifested biochemically and histopathologically. Pre-treatment with sodium bicarbonate or theophylline partially ameliorated the CIN. While, combined administration of sodium bicarbonate and theophylline before urografin injection showed marked improvement of renal function and histopathological examination in rats.