Haptoglobin is a hemoglobin-binding acute-phase protein which possesses anti-inflammatory and antioxidative properties. In this study, we investigated changes in protein expression of rat haptoglobin under diabetes-related inflammatory and oxidative stress conditions induced by an i.p. injection of streptozotocin. The progress of diabetes during an 8-week follow-up period was associated with the increased presence of haptoglobin in the serum and in the liver. This increase was most prominent during the first 2 weeks after which it started to decline. Temporary changes in haptoglobin expression strongly correlated with the serum levels of TNF-α and IL-6. Lower haptoglobin expression at the fourth week and thereafter correlated with a decrease in TNF-α concentration and changes in the TNF-α/IL-6 ratio. Based on the decrease of GSH/GSSG ratio and antioxidant enzyme activities in the liver until the end of fourth week, it was concluded that the liver was exposed to oxidative stress and injury which in the presence of the above-mentioned inflammatory mediators lead to different haptoglobin expression profiles at different stages of diabetes. An inverse correlation was observed between the haptoglobin and free iron serum levels in diabetic rats. The higher levels of haptoglobin during the first 2 weeks were accompanied by a lower level of free iron. In view of the established function of haptoglobin, we discuss its possible role in decreasing oxidative stress during the early stage of diabetes.