Aims This study was designed to prepare chrysophanol-loaded micelles (CLM) to improve the oral bioavailability, targetability and anti-chronic renal failure (CRF) activity of chrysophanol (CH). Methods The preparation of CLM was achieved via thin-film dispersion technique. The in vitro release of CLM compared with free CH was measured in phosphate buffer solution (PBS) containing 0.5%w/v sodium dodecyl sulphate (pH 6.8) while the pharmacokinetic and anti-CRF activity study was also conducted in rats. Moreover, the tissue distribution of CLM was investigated in the mice. Results The CLM had particle size (PS) of 29.64 +/- 0.71 nm, and encapsulation efficiency (EE) of 90.48 +/- 1.22%w/w. The cumulative release rate of CH from the micellar system was significantly higher than that of the free CH (86%m/m vs. 15%m/m, p < 0.01). In vivo pharmacokinetic studies showed that the bioavailability of CLM after oral administration was substantially improved (about 3.4 times) compared with free drugs (p < 0.01). Also, it was observed that CLM accumulated well in the liver and brain. Moreover, in vitro renal podocytes study showed that CLM had better protection against renal podocyte damage than the free CH. In addition, CLM significantly (p < 0.01) reduced levels of blood urea nitrogen (BUN), kidney injury molecule-1 (Kim-1), and serum creatinine (SCr), which obviously improved kidney damage in rats with CRF. Conclusions Collectively, these findings suggest that mixed micelles may be used as a promising drug delivery system for oral bioavailability improvement and concomitantly enhance the anti-CRF activity of CH, as well as provide a basis for the clinical application of CH.