Backgrounds Dyrk1a (the dual specificity tyrosine phosphorylation-regulated kinase 1A) is an enzyme that in humans is encoded by the DYRK1A gene. Dyrk1a is a member of the DYRK family which plays key roles in the control of cell proliferation and differentiation. Dyrk1a is known for their importance in body growth and brain physiology. Previous studies have shown that homozygotes knockout mice are embryonic lethal, though haploinsufficiency of Dyrk1a leads to developmental delay and decreased brain size in mice. To investigate the effect of the knockdown of Dyrk1a in rats is identical which observed in mice, we generated genetically engineered rat model of haploinsufficiency of DYRK1A gene. Methods To figure out the roles of DYRK1A gene, we induced Dyrk1a knockdown rats by deleting 11 nucleotides in exon 7 using CRISPR/Cas9 system. We selected a target showed higher efficiency in their activity for generating Dyrk1a haploinsufficiency rats. Oocytes were collected from hyper-ovulated female SD rats, and genetically modified by micro-injection of purified RNA and CRISPR/Cas9 protein. Results We performed embryo transfer to surrogate female rats 5 times and got 6 to 14 pups per one recipient rat. Dyrk1a haploinsufficiency rats showed smaller body size and decreased brain size compared to wild-type rats. The protein level of sirtuin1(SirT1) phosphorylated by Dyrk1a also decreased in the brain of knockdown rats. Seeing that the protein level of signal transducer and activator of transcription3(STAT3) was also decreased, it suggests that SirT1 and STAT3 activities in brain are down-regulated in Dyrk1a haploinsufficiency rats. Conclusion The results obtained in this study indicate that Dyrk1a haploinsufficiency rats showed comparable phenotype with mice. The exact molecular and cellular mechanisms that are targeted by the inhibition of Dyrk1a are still to be discovered. Rats are more preferred to study in brain diseases, we propose this model can be a powerful tool in brain research such as Autism and Alzheimer’s.