In Vivo: GW788388 given orally for 5 weeks significantly reduces renal fibrosis and decreased the mRNA levels of key mediators of extracellular matrix deposition in kidneys in db/db mice. GW788388 (50 mg/kg/day, p.o.) significantly attenuates systolic dysfunction in the MI animals, together with the attenuation of the activated (phosphorylated) Smad2 (P < 0.01), α-smooth muscle actin (P < 0.001), and collagen I (P < 0.05) in the noninfarct zone of MI rats. GW788388 reduces the expression of collagen IA1 by 80% at a dose of 1 mg/kg twice a day (b.i.d.). GW788388 significantly reduces the expression of collagen IA1 mRNA when administered orally at 10 mg/kg once a day (u.i.d.) in a model of puromycin aminonucleoside-induced renal fibrosis.