Abstract: The full-length cDNA sequence of Calreticulin CRT gene was isolated from the mantle of Hyriopsis cumingii by using homology cloning strategy and SMART RACE technique. The entire CRT cDNA was 1838 bp, containing a 1257 bp complete open reading frame which encoding a protein with 418 amino acids, a 75 bp 5' UTR, and a 506 bp 3' UTR (GenBank accession number is JX416227). Bioinformatics analysis indicated that the calreticulin gene had a signal peptide, two typical calreticulin family labels (KHEQNIDCGGGY and MFGPDICG), three conserved domains (N-, P-, and C-), and the endoplasmic reticulum retrieval sequence HDEL. Phylogenetic analysis indicated that the CRT gene of H. cumingii was closely related to seawater bivalves, followed by that of annelidas and then fish, amphibians, and mammals. Real-time PCR revealed that CRT genewas ubiquitously expressed in all tested tissues, but far more abundant in tissues that closely relating to calcium metabolism such as mantle, gill and foot. This result indicates an intrinsical relationship between CRT gene and calcium metabolism in H. cumingii. When exposed to a serie of increasing Ca2+, the mRNA expressionof CRT gene in mantle was shown to be bell-shaped, ascending when Ca2+concentration was less than 60 mg/L and descending when Ca2+concentration was greater than 60 mg/L. The result that CRT gene expression reached its maxium when exposed to 60 mg/L Ca2+, suggesting appropriate Ca2+ concentration would stimulate the expression of CRT gene. Moreover, as the Ca2+ (60 mg/L) exposure time increased, the CRT gene expression in mantle was shown to increase initially, reach its peak at 48h, and then decrease subsequently. The results of present study will provid useful information for further studies on function and regulation mechanism of CRT gene.