Background Increasing peritoneal permeability with ultrafiltration and solute removal inadequacy is a challenging issue in peritoneal dialysis (PD). Decreasing permeability is less frequent but also results in diminished solute clearance. We evaluated the association between longitudinal high-sensitive C-reactive protein (hs-CRP) values and the change in transport characteristics of the peritoneal membrane in PD patients. Methods This is a retrospective, single-center study of incident PD patients. An increase or decrease in peritoneal transport status is defined as two or more categories of a rise or decline in the peritoneal equilibration test (PET) from their baseline during follow-up. The 4-h dialysate/plasma creatinine ratio was used to classify transport characteristics. Hs-CRP values were obtained from the routine annual examinations of the patients. Results Baseline demographics, residual kidney function, frequency of high glucose-containing dialysate, and icodextrin use were similar between the groups. Total episodes of peritonitis within the first 5 years of follow-up were higher in stable transporters than in increased and decreased transporters (p = 0.009). Stable transporters' mean hs-CRP values did not change within 5 years (Wilks' lambda = 0.873, F (2.317, 180.740) = 2.210, p = 0.10). Increased and decreased transporters' hs-CRP values significantly raised over the years (Wilks' lambda = 0.422, F (1.979, 77.163) = 3.405, p = 0.04 and Wilks' lambda = 0.558, F (3.673, 66.107) = 4.396, p = 0.001, respectively). Conclusions Our study shows that the peritoneal membrane may change into different characteristics in many patients over time, despite very low peritonitis frequencies and similar baseline characteristics that may be significantly affected by systemic inflammation.