The aim of this study was to investigate whether bevacizumab and everolimus combination therapy is superior to bevacizumab treatment alone as a treatment for peritoneal sclerosis. Forty Wistar albino rats were divided into five equal groups. The control group received isotonic saline solution (2 mL/day) intraperitoneal (IP) daily for 3 weeks. The CG group received 2 mL 0.1% chlorhexidine gluconate (CG) and 15% ethanol dissolved in saline IP daily for 3 weeks. Peritoneal tissue samples were taken at the end of 3 weeks. The resting group received CG (weeks 0-3), plus isotonic saline solution (2 mL/day) IP daily and tap water (2 mL/day) via a feeding tube daily (weeks 3-6).The bevacizumab group received CG (weeks 1-3) plus bevacizumab at 2.5 mg/kg/day (2 mL) IP daily and tap water (2 mL/day) via a feeding tube daily (weeks 3-6). The bevacizumab+everolimus group received CG (weeks 1-3) plus bevacizumab at 2.5 mg/kg/day (2 mL) IP daily and everolimus at 0.3 mg/kg/day (2 mL) via a feeding tube daily (weeks 3-6). Peritoneal tissue samples were taken from these three groups at the end of 6 weeks and were examined after staining with hematoxylin-eosin and Masson's trichrome. Inflammation, vasculopathy, fibrosis, and peritoneal thickness were evaluated under light microscopy. The samples were also stained with anti-TGF-β and anti-MMP-2. Inflammation and vasculopathy scores were significantly decreased in the VEGF-i group compared to the CG group. The addition of everolimus to VEGF-i showed significantly lower inflammation, vasculopathy, fibrosis scores, and an evident decrease in peritoneal thickening (respectively, 2.29 ± 0.76 vs 0.57 ± 0.53, P = .003; 2.71 ± 0.76 vs 1.43 ± 0.53, P = .008; 2.57 ± 0.79 vs 1.57 ± 0.79, P = .04; 247.5 ± 136.1 vs 84.5 ± 48.6, P = .048). MMP-2 levels were lower in the combination group compared to the resting group (2.63 ± 0.74 vs 1.86 ± 0.38, P = .019). The study results demonstrated that bevacizumab and everolimus combination therapy was more effective than bevacizumab therapy alone., (© 2020 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)