Identification of drowning in freshwater or saltwater still controversial. The recovered bodies form water and movement of cadavers made the task of differentiation of two types of drowning so difficult. To better understand the pathophysiology and PMI changes in drowning, we use 36 albino rats were exposed to induction of drowning in freshwater and or saltwater and recovered bodies were kept to 24 or 48 hrs for checking the changeable PMI markers between fresh or saltwater. Notably, brain of saltwater drowning show severe vacuolation in the brain parenchyma, heart is showing death of cardiomyocytes and increases in the interstitial spaces and lung displays pulmonary atelectasis and over distended alveoli with air with rupture of capillaries and cellular death of interstitial cells. While this pathological feature in freshwater is less prominent than saltwater. Fresh water drowned rats showed an increase in level of LDH, Albumin, total protein, sodium, potassium and chloride in postmortem time dependent manner.Notably, cholesterol and CPK were fluctuated levels in fresh water drowned rats and levels of triglycerides and calcium were time dependent decreased. However, drowning in saltwater, retard analysis and protein degradation in first 24 after rat's corpse recovered from water, then again started with evidence of increase total protein and albumin. While LDH and sodium were increased until 24hrs and then decreased. Moreover, there were a time dependent increase of triglycerides, CPK and calcium in postmortem drowned rats in saltwater and decreased the level of cholesterol, potassium and chloride in the water drowned rats. Intriguing, that collagen deposition and immunostaining reaction of IL-6 considered as a good marker for differentiation of tissue of lung and heart between different causes of death as it increased in saltwater >fresh> natural induced death. In conclusion, biochemical markers of PMI are causes of death dependent and could differ from case to another. often a difficult task, as the typical features of pulmonary edema