ONO-1301MS is a compound that acts as a prostacyclin agonist with thromboxane A2 synthase inhibitory activity. We investigated the effect of ONO-1301MS on myocardial remodeling in murine cardiac allografts. The hearts of Balb/c mice were transplanted into C3H/He mice (a full allomismatch combination) to assess acute rejection or C57BL/6 hearts into B6.C-H2^‹bm12› KhEg (a class II mismatch combination) to examine chronic rejection. ONO-1301MS did not prolong full allomismatch cardiac graft survival. Severe myocardial fibrosis with high collagen concentration was observed in untreated class II mismatch allografts on day 60. However, significantly suppressed myocardial fibrosis with less collagen synthesis was observed in the ONO-1301MS-treated group compared to the control group. ONO-1301MS could be an effective strategy to suppress chronic myocardial remodeling in cardiac transplantation.