In this paper, four kinds of collagen-based leather filling materials, namely collagen-based amino resin (MCL), collagen-based acrylic resin (NCL), collagen-based hyperbranched resin (HCL), and aliphatic collagen-based resin (ACL) were prepared by our laboratory and applied in filling process of cattle upper leather. Herein, the stability of the four materials and the physical and mechanical properties of retanned leather using these four materials were detailed evaluated. The experimental results showed that all the four materials had excellent compatibility with salt, aldehyde and acrylic resin, and have certain flocculation with condensed tannin (chinese bayberry extract, wattle extract). When these four materials are applied in filling process, compared with the controlled leather, the leather filled with MCL felt more tight and had obvious thickening effect. Moreover, shrinkage temperature of the leather filled with ACL and NCL increased significantly. The tensile strength of the leather filled with HCL increased by 35.9%. The tear strength of the leather filled with ACL increased by 40.0%, and the usage of ACL can promote the absorption of dyes, the total organic carbon in wastewater reduced by 29.5%.