The permeability of a weak polyelectrolyte ultrafiltration membrane based on poly(acrylonitrile and 2-dimethylaminoethyl methacrylate) (PAN-DMAEMA) copolymer was measured at various conditions of solution pH and ionic strength. Bovine serum albumin (BSA) and lysozyme were used as model proteins to investigate the antifouling property of PAN-DMAEMA ultrafiltration membrane. Electrostatic interactions, the conformation of PDMAEMA chains, and the nature of protein play important roles in enhancing the antifouling property of PAN-DMAEAM membrane. During BSA ultrafiltration, BSA rejection ratio is decreased, flux recovery ratio is remarkably increased, and the total membrane fouling and irreversible membrane fouling are decreased at higher pH value and ionic strength. During lysozyme ultrafiltration, the PAN-DMAEAM membrane displays excellent antifouling property in a broad range of pH and ionic strength.