To evaluate the compatibility and the pharmacokinetic (PK) properties of a combination of marbofloxacin and imipenem administered by regional limb perfusion (RLP) to standing horses and to determine if the concentrations of imipenem in the synovial fluid would be as high as when imipenem was administered alone. Experimental study—Six healthy, adult horses participated in the study; that was approved by the University Animal Care and Use Committee. Under sedation, a tourniquet was applied on one, randomly selected forelimb. One gram of marbofloxacin and 500 mg of imipenem diluted to 100 mL were injected, into the cephalic vein, using a 22g butterfly catheter. Synovial samples were collected from the metacarpophalangeal (MCP) joint and blood samples were collected from the jugular vein on times: 0, 0.5 (tourniquet release time), 2, 6, 12, 24, and 36 hours after injection. All samples were analyzed for marbofloxacin and imipenem concentration using liquid chromatography tandem mass spectrometry. Maximum concentration (Cmax) of imipenem and marbofloxacin in the MCP joint was 71 and 73 μg/mL, respectively. No significant differences in PK values were detected when this study results were compared with the results of a previous study evaluating the PK of imipenem administered alone by intravenous (IV) RLP. This study results indicate that combining imipenem with marbofloxacin during IV-RLP in normal horses delivered high therapeutic concentrations of both drugs and that the combination does not negatively affect the concentration of imipenem attained in the synovial fluid.