Dichloro(1,2-diaminocyclohexane)platinum(II)(DACHPt), a cisplatin(CDDP) analog, has shown lower toxicity than CDDP and no cross-resistance with CDDP in many CDDP-resistant cancers. PEGylated hyaluronan(m PEG-HA) is an m PEG conjugated with hyaluronan biodegradable polymer which is a naturally occurring biopolymer in the interstitium, is primarily cleared by the lymphatic system. m PEGhyaluronan–DACHPt(PEG-HA–Pt) conjugate could circulate long-term in the bloodstream and increase DACHPt concentration in the tumor site and decrease systemic toxicity. m PEG-HA conjugates with the range of 1%–5% substitution were synthesized, and the structures were confirmed by1 H NMR and IR. The particle size of DACHPt incorporated with m PEG-HA was about 86 nm and the loading content and efficiency were about 19%(w/w) and 86%, respectively. The synthesized m PEG-HA with different PEG substitution degrees presented non toxicity, and the cell viability of DACHPt loaded in m PEG-HA nanoparticles increased with increasing doses of DACHPt. DACHPt release from nanoparticles slightly decreased with increasing PEG substitution degree from 1% to 5% at 37 8C, pH 7.4 PBS solution. The DACHPt loaded in m PEG-HA nanoparticles significantly inhibited the growth of A549 xenografts in nude mice when compared to the DACHPt loaded in HA nanoparticles and the control group after 4 weeks treatment(p < 0.01 compared with control). The body weight change curve shows that the mice weight loss was less than 5% by treating with both DACHPt loaded in m PEG-HA and HA nanoparticles. In conclusion, a novel DACHPt loaded m PEG-HA delivery system was developed with sustained release and increased platinum concentration in the tumor. Dichloro (1,2-diaminocyclohexane) platinum (II) (DACHPt), a cisplatin (CDDP) analog, has shown lower toxicity than CDDP and no cross-resistance with CDDP in many CDDP-resistant cancers. PEGylated hyaluronan ) is an m PEG conjugated with hyaluronan biodegradable polymer which is a naturally occurring biopolymer in the interstitium, is primarily cleared by the lymphatic system. m PEGhyaluronan-DACHPt (PEG-HA-Pt) conjugate could circulate long-term in the bloodstream and increase DACHPt concentration in the tumor site and decrease systemic toxicity. M PEG-HA conjugates with the range of 1% -5% substitution were synthesized, and the structures were confirmed by1H NMR and IR. The particle size of DACHPt incorporated with m PEG- HA was about 86 nm and the loading content and efficiency were about 19% (w / w) and 86% respectively. The synthesized m PEG-HA with different PEG substitution degrees presented non-toxic, and the cell viability of DACHPt loaded in m PEG-HA nanoparticles incr eased with increasing doses of DACHPt. DACHPt release from nanoparticles with reduced increasing PEG substitution degree from 1% to 5% at 37 8C, pH 7.4 PBS solution. The DACHPt loaded in m PEG-HA nanoparticles significantly inhibited the growth of A549 xenografts in nude mice when compared to the DACHPt loaded in HA nanoparticles and the control group after 4 weeks treatment (p <0.01 compared with control). The body weight change curve shows that the mice weight loss was less than 5% by treating with both DACHPt loaded In conclusion, a novel DACHP loaded II PEG-HA delivery system was developed with sustained release and increased platinum concentration in the tumor.