To study the long-term effects of dialysis fluids on the peritoneal cavity, an in vivo model for continuous peritoneal dialysis in rats was developed. Mini vascular access ports were implanted subcutaneously in the neck of the rats and an attached catheter was instilled into the peritoneal cavity. Rats were injected daily with 10 mL of standard 3.86% Dianeal or saline for a period up to 12 weeks. In the peritoneal cavity an initial increase in total cells was observed after 4 weeks of fluid instillation. This had declined after 12 weeks. A similar trend was also seen for macrophage and neutrophil numbers, whereas the percentage of lymphocytes kept increasing in time. An effect of fluid instillation was observed on the density and the morphology of the mesothelial monolayer of the rats. A higher density of cells was observed after 12 weeks, and foci of young mesothelial cells within activated mesothelium were found. The results show that the rat model presented can be compared with the situation in the peritoneal cavity of continuous ambulatory peritoneal dialysis (CAPD) patients, and therefore is suitable for intervention studies.