Hyaluronic acid (HA) nanogel is derived by the partial modification of hyaluronic acid with cholesterol, causing the formation of self-assembled nanometer-scale hydrogel in water. Thus, HA nanogels might contribute to alter drug delivery of poorly water-soluble drugs. In this study, we tried to investigate the effect of HA nanogels by using cyclosporine (CyA) in rats. HA nanogels (Asahi Kasei Co, 5 mL/kg) containing CyA (2.5-15 mg/kg) were subcutaneously administered in male SD rats (Charles River) and whole blood samples were collected at the designated time-points up to 28 days. The concentrations of CyA were measured using LC-MS/MS 6045 (Shimadzu). In rats administered CyA without HA nanogel (control group), the concentration of CyA was below the detection limit (3 ng/mL) on 7 days after administration. Some formulas of HA nanogel showed the sustained-release properties of CyA. Interestingly, one formula could be detectable up to at least 10 days after administration. HA nanogels would be useful as a tool to alter drug delivery of poorly water-soluble drugs such as CyA.