Objective] To explore the humoral and cellular immune responses in mice to eukaryotic expression recombinant plasmid encoding histidine rich protein 2 (HRP\|Ⅱ) of Plasmodium falciparum. [Methods] The start and stop codes were introduced into HRP\|Ⅱ gene fragment, the reading frame and the position of start and stop codes in HRP\|Ⅱ were identified by sequencing. HRP\|Ⅱ fragment containing the start and stop codes was cloned into pcDNA3 1(\|) to form pcDNA3 1(\|)/HRP\|Ⅱ. The BALB/c mice were immunized i.m. with the plasmids for 3 times in 3 weeks intervals. Two weeks after the last immunization, the sera and splenocytes were collected to investigate anti\|HRP\|Ⅱ antibodies by ELISA and the splenocytes proliferation response to HRP\|Ⅱ. [Results] Sequence data show that the reading frame and the position of start and stop codes are correct. Restriction enzyme digestion indicated that the HRP\|Ⅱ gene fragment containing start and stop codes was successfully cloned into pcDNA3 1(\|). Mice raised significant anti\|HRP\|Ⅱ antibodies after pcDNA3 1(\|)/HRP\|Ⅱ immunization, and the splenocytes proliferated prominently when stimulated with HRP\|Ⅱ protein. [Conclusion] Eukaryotic expression recombinant plasmid \{encoding\} HRP\|Ⅱ gene can induce significantly humoral and cellular immune response in mice. HRP\|Ⅱ gene may be a good candidate for P.falciparum blood\|stage multiple DNA vaccine.