Type 2 diabetes is associated with cardiomyopathy. Chronic hyperglycemia and activation of the renin‐angiotensin system lead to oxidative stress, excessive collagen accumulation and myocardial dysfunction. The cardiac collagen network is produced primarily by cardiac fibroblasts (CF). This study examined alterations in basal activation of signaling cascades and expression of pro‐fibrotic markers within the myocardium of diabetic (db/db) mice compared to non‐diabetic (Db/db) littermates. In vivo functional analysis with conductance catheters indicated decreased compliance (end diastolic pressure‐volume relationship) that correlated with increased collagen deposition in db/db hearts. Primary cultures of CF were isolated from both groups. Protein analysis demonstrated increased expression of type I collagen, TIMP‐2, TGF‐beta and PAI‐1 in db/db cells vs. Db/db. Moreover, iNOS and RAGE protein levels were elevated in db/db CF compared to Db/db. These changes occurred independently of glucose concentration in the media. This pattern of protein expression was associated with basal activation of ERK1/2 MAP kinases and SMAD 2/3. These studies demonstrate a distinct role for myocardial fibroblasts in establishing and maintaining a fibrotic environment in diabetic cardiomyopathy. Supported by HL056046, R01HL063318 and P20RR18766 (PAL).