In plants, Ca2+-dependent protein kinases (CDPKs) are characterized as important sensors of Ca2+ flux in response to varieties of biotic and abiotic stress. A comprehensive survey of global gene expression performed by using an Arabidopsis thaliana whole genome Affymetrix gene chip revealed that CDPK tends to be significantly higher in tetraploid Isatis indigotica than in diploid ones. To investigate different CDPK expression in response to polyploidy, a full-length cDNA clone (IiCPK1) encoding CDPK was isolated from the traditional Chinese medicinal herb I. indigotica cDNA library. IiCPK1 contains some basic features of CDPKs: a catalytic kinase domain including an ATP-binding domain and four EFhand calcium-binding motifs. Real-time PCR analysis indicated the expression of IiCPK1 from two kinds of I. indigotica (tetraploid and diploid). They both were induced in response to cold stress, but tetraploids I. indigotica which has good fertility, exhibited an enhanced resistance and higher yield, and presented to be more responsive and adaptable. Our results suggest that IiCPK1 gene plays a role in adapting to the environmental stress.