Experimental studies demonstrated antibodies against matrix and coating of polyester‐based vascular prostheses. Thus, this study examined associations of these antibodies with serum cytokines (IL‐2, IL‐4, and IL‐10) and local inflammatory reactions. Rats (n = 8/group) intramuscularly received prosthesis segments [PET‐C, PET‐G, and PET‐A groups: polyethylene terephthalate (PET)‐based prostheses coated with bovine collagen and gelatin or human serum albumin, respectively; uncoated polytetrafluoroethylene‐based (PTFE) prosthesis], with sham‐operated controls. Blood was drawn pre‐operatively and weekly until day 22. Polymer‐specific or coating‐specific antibodies and cytokines were detected by enzyme immunoassays, inflammatory reactions were immunohistochemically evaluated on day 23. Polymer‐specific antibodies were detected in all PET‐groups using uncoated PET as antigenic target, but not for PTFE or controls, coating‐specific antibodies only for PET‐A. IL‐10 was increased in all PET‐groups and correlated with polymer‐specific antibodies for PET‐G and PET‐A. IL‐2 was increased for PET‐A, but overall correlated with PET‐specific antibodies. IL‐4 remained unchanged in all groups. Intense local inflammatory reactions (ED1+/ED2+ macrophages and T lymphocytes) were found within all PET‐groups, but only minor for PTFE or controls. In conclusion, PET‐specific antibodies were associated with increased IL‐10 and along with concurrent coating‐specific antibodies also with increased IL‐2, indicating a specific T cell response. Thus, matrix and/or coating of polymeric vascular prostheses elicit distinct systemic immune reactions, probably influencing local inflammatory reactions.