Objective: The aim of the present investigation was to evaluate the cyototoxic effect of commonly used neoplastic drugs including adriamycin, cisplatin and 5-FU. Methods: Twenty-four mature male albino rats weighing approximately 130-150 g body weight were arranged into four groups; control, adriamycin (0.2 mg/kg.b.wt), cisplatin (0.2 mg/kgb.wt.) and fluorouracil (20 mg/kg. b.wt.). The applied dose was intraperitoneally injected every other day for 21 days. Isoenzyme electrophoresis of alkaline-acid phosphatase, lactic dehydrogenase and glucose 6-phosphate dehydrogenase were investigated using electrophoresis. As well as, plasma content of vascular endothelial growth factor (VEGF), heat shock protein 70 (HSP-70), troponin-t, 8-hydroxy-2′-deoxyguanosine (8-OHdG), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) was measured by ELISA. Results: Different chemotherapeutic treatments exhibited alterations of the activity of isoenzymes including acid phosphatase, lactic dehydrogenase and glucose 6 phosphate dehydrogenase. As well as a significant reduction in serum contents of VEGF, HSP-70, bICAM-1 and VCAM-1, in contrary, an increase in troponin-t and 8-OHdG were observed. The present findings concluded that chemotherapeutic treatment interfere with cell function causing alterations in isoenzymes and reduction of cell growth by decreasing of VEGF, HSP-70 and cell adhesion molecules. As well as predict of cell damage as detected by increase of serum troponin-t and 8-OHdG.