We previously reported that 2, 5-dimethylcelecoxib (DMC), a derivative of celecoxib, suppresses cardiac remodeling by suppression of fibroblast-myofibroblast transformation. However, its effects on the immunoreactive responses remain unclear. As macrophages are known to play critical roles in the process of fibrosis after myocardial damage, we evaluated the effect of DMC on macrophages using a cryoinjury-induced myocardial infarction (CMI) model mouse. The anterior left ventricular was cryo-injured by a liquid nitrogen-cooled aluminum probe in male C57 BL/6 mice. The mice were provided feed containing DMC or vehicle starting 3 days before the operation. Echocardiography showed that DMC attenuated the impairment of cardiac function, and Masson’s trichrome staining of cross-section heart showed DMC reduced fibrosis area at the 14 days post-operation. In the cryo-injured damage area, DMC increased CD163-positive anti-inflammatory (M2) macrophages 3 days after operation, but not CD86-positive pro-inflammatory (M1) macrophages. Real-time PCR showed that DMC suppressed mRNA expression of interleukin (IL) -1β, IL-6, and monocyte chemoattractant protein (MCP) -1, which are known as inflammatory cytokines, in the damaged myocardium. These results suggested that DMC could attenuate impairment of cardiac function and fibrosis after the cardiac damage through increasing accumulation of M2 macrophages and decreasing inflammatory cytokines. Thus, DMC has potential against cardiac fibrosis and could be useful for the treatment of cardiac remodeling.