Inhibition of FXa by administration of edoxaban ameliorated diabetic nephropathy in the eNOS−/− DM mouse model and reduced the expression of the profibrotic and pro-inflammatory genes Pai1, Col1, Col4, and Tnfa as well as expression of Par1 and Par2. Par2 expression in the kidneys was increased in eNOS−/− DM mice, and lack of Par2 was shown to also ameliorate diabetic nephropathy. Here, NOS3 is linked to diabetic kidney disease.