Heparin can cause some complications in tissues when it is used for long-term therapy. Besides its beneficial effects, it may have some side effects. In this study, we investigated the possible hematological and histopathological changes in rabbit tissues under long-term (1 month) and overdoses (1,000 and 2,000 IU/kg/day) heparin applications. Group 1 was injected with serum physiologic and kept as control while Groups 2 and 3 were injected with heparin as dosages of 1,000 IU/kg/day and 2,000 IU/kg/ day, respectively. There were no significant differences between the average values of serum electrolytes and copper levels and liver enzymes ALT, AST of 2 experimental groups and the control group while their serum zinc levels (4.54 +/- 0.52 mug/ml and 4.72 +/- 0.65 mug/ml) were significantly (p < 0.05) lower than the controls (5.75 +/- 0.72 mug/ml). Hemoglobin level of Group 3 was significantly lower than of Group 2 and the control. In light microscopy, investigation of liver tissues of Groups 2 and 3, we observed mainly some disturbances in vascular outflow, disruption of normal histologic organization resulting in loss of cord architecture, intralobular inflammation with disruption of cords. Focal necrotic areas with eosinophilic amorphous materials in aortic tissue and edema, enlarged perivascular areas and interstitial tissue with scattered lymphocyte in myocardium were observed in Group 2. Degenerative regions with amorphous materials and calcification like atheroma plaque in aorta, some necrotic cells in myocardium were observed in Group 3. In lung tissues from Groups 2 and 3, interstitial imflammation, widened and densely infiltrated interalveolar septa and necrotic cells in the alveoles were seen. Alveoli were also dilated and filled with edema fluid. These findings suggest that long-term and overdose heparin application have degenerative side effects on tissues and especially on serum zinc level.