AKI in patients with pre-existing CKD have increased co-morbidity and mortality. Although it is well established that AKI is associated with a major increase in pro-inflammatory cytokines and chemokines, it is unknown to which extent AKI in pre-existing CKD leads to changes in the expression of proinflammatory cytokines/chemokines. The aim of this study was to assess the changes in the expression of pro-inflammatory cytokines and chemokines in kidney and lung in response to AKI in rats with pre-existing CKD. CKD was induced by 5/6 nephrectomy (5/6 Nx) for 6 weeks. AKI was induced by intestinal ischemia for 45 min followed by reperfusion for 90 min (II/R): 1) Nx+II/R; 2) Sham Nx+II/R; 3) Nx+Sham II/R; 4) Sham Nx+Sham II/R, 5) controls. Cytokines/chemokines were measured in homogenized whole kidney and lung preparations with LuminexTM 100. S-Cr increased significantly in response to II/R:from 66.2±7.3 to 88.9±8.3 in Nx rats, resp., and from 32.0±0.7 to 54.7±2.9 in Sham Nx rats. The levels of IL-1b, IL-6, RANTES, and MCP-1 in lung and kidney, were significantly higher in rats undergoing II/R compared to sham II/R. Importantly also in the 5/6 Nx rats II/R induced a significant increase in IL-1b, IL-6, RANTES, and MCP-1 expression in kidney and lung compared to sham 5/6 Nx. Morever the response was even more pronounced in the 5/6 Nx compared to the response in sham 5/6 Nx rats. The results demonstrate a significant increase in pro-inflammatory cytokines and chemokines in response to AKI in rats with pre-existing CKD.