Water-soluble hyper-branched poly(ethylenimine)-graft-poly(caprolactone)-block-monomethoxyl-poly(ethy lene glycol) cationic copolymers (hy-PEI-PCL-mPEG) have shown potential for gene delivery. The degradation behavior of this type of copolymer is studied. Effects of the molecular weight of the hyper-branched PEI (hy-PEI), and the length of the mPEG and PCL blocks are investigated. The degradation is mainly monitored by the changes of molecular weight by GPC-MALLS. The molecular weight changes of the copolymers in different aqueous solutions have been characterized as a function of incubation time at 37 degrees C from 0 to 45 d. The micelle size and pH value have also been recorded accordingly to monitor the degradation in water. The investigation reveals that copolymers containing hy-PEI2k degrade faster than others containing hy-PEI10k and hy-PEI25k based on the same mPEG-PCL block, while copolymers those contain mPEG5k degrade faster than those containing mPEG2k and mPEG0.55k based on the same PCL segments and hy-PEI. An inhibitory effect of acidic conditions and acceleration in basic media have been found for degradation in different buffers. A higher ionic strength of the buffer accelerated the degradation. The molecular weight of copolymer is reduced to 95% within one day with 10 mg . mL(-1) of lipase while 70% remains with 5mg . mL(-1) of lipase. These investigations suggest that the degradation of hy-PEI-PCL-mPEG can be designed and the degradation period is reasonable for gene-transfer in vivo.