Objective To investigate the serum level of angiotensin Ⅱ type 1 receptor (AT₁R) agonistic autoantibody (AT₁-AA) in hyperthyroidism rats with cardiac hypertrophy and the expression of PI3K and protein kinase B (Akt) in cardiac tissue, so as to study the relationship between AT₁-AA and PI3K/Akt signaling pathway. Methods Hyperthyroidism rats models were established by gavaging with levothyroxine sodium. Totally 54 SD rats were divided into three groups: hyperthyroidism group(group A), hyperthyroidism+olmesartan group(group B) and control group (group C). The heart weight index (HWI) and atrial natriuretic peptide (ANP) mRNA were taken as the indices for cardiac hypertrophy. Serum AT₁-AA level was determined by enzyme-linked immunosorbent assay (ELISA), and the expression of AT₁R and PI3K/Akt was detected by Western blotting analysis. According to the determination results of AT₁-AA, group A and B rats were subdivided into AT₁-AA positive group and negative group; the expressions of AT₁R and PI3K/Akt were compared between these groups. Results (1) Compared with group C, HWI and the expression of ANP mRNA in group A and B were significantly increased (all P<0.05); and those in group A were significantly higher than those in group B (P<0.05). (2) The positive rates and OD values of AT₁-AA in group A and B (61.11%, 72.22% and 0.44±0.12, 0.49±0.08) were significantly higher than those in group C (16.67% and 0.28±0.05) (all P<0.01).(3)The expressions of AT₁R and PI3K/p-Akt in group A and B were significantly higher than those in group C (P<0.05, P<0.01). Compared with group A, the expression levels of PI3K, p-Akt were significantly decreased in group B (P<0.01, P<0.05). (4) In group A, the expression levels of PI3K and p-Akt in AT₁-AA positive group were significantly higher than those in AT₁-AA negative group(P<0.01); in group B, the expression levels of PI3K and p-Akt in AT₁-AA positive group were significantly decreased than those in AT₁-AA negative group (P<0.05). Conclusion AT₁-AA may be involved in the pathophysiology of cardiac hypertrophy in hyperthyroidism by activating PI3K/Akt signaling pathway through AT₁R.