Background and Objectives: Aquaporins are a family of water channel proteins. In this study, the renal and intrapulmonary expression of aquaporin-5 (AQP5) was examined in forensic autopsy cases to evaluate it as a drowning marker and to differentiate between freshwater drowning and saltwater drowning. Materials and Methods: Cases were classified into three groups: freshwater drowning (FWD), saltwater drowning (SWD), and controls (CTR). Samples were obtained from forensic autopsies at less than 72 h postmortem (15 FWD cases, 15 SWD cases, and 17 other cases) and were subjected to histological and immunohistochemical investigations. Results: In FWD group, intrapulmonary AQP5 expression was significantly suppressed compared with SWD and CTR; there was no significant difference in AQP5 expression among the other two groups. The same differences in expression were also observed in the kidney. Conclusions: These observations suggest that AQP5 expression in alveolar cells was suppressed by hypotonic water to prevent hemodilution. Moreover, it is possible to hypothesize that in the kidney, with the appearance of hypo-osmotic plasma, AQP5 is hypo-expressed, as a vital reaction, to regulate the renal reabsorption of water. In conclusion, the analysis of renal and intrapulmonary AQP5 expression would be forensically useful for differentiation between FWD and SWD, or between FWD and death due to other causes.