This retrospective study is designed to evaluate the diagnostic value of semi-quantitative parameters of salivary gland scintigraphy (SGS) in Sjögren's syndrome (SS) and explore the relationship between SGS parameters and salivary gland histopathologic manifestations. SGS and labial salivary gland biopsy were performed on 95 SS patients and 36 healthy age-matched and sex-matched volunteers. Uptake ratios at 15 min (UR(15)) and stimulated excretion fraction (EF) of each parotid and submandibular gland were calculated automatically from SGS; histopathologic grades were classified based on focal lymphocytic infiltration, and biopsy focus scores were calculated simultaneously. As a result, the UR(15) and EF of each salivary gland in SS patients were significantly lower than that in controls. Multivariate logistic regression equation was: logit p = 6.965 - 1.680 × UR(15) of left submandibular gland - 0.040 × EF of left parotid gland - 0.050 × EF of right submandibular gland. The receiver operating characteristic (ROC) curve validated high efficiency of this model with the area under curve of 0.911. And logistic regression analysis on combined original and validation cohorts confirmed its diagnostic value. Moreover, the EF of right parotid gland and both submandibular glands was correlated with histopathologic changes. Consequently, the semi-quantitative parameters of SGS may be helpful for diagnosing SS; UR(15) of left submandibular gland, EF of left parotid gland, and EF of right submandibular gland are more powerful predictor of SS. Besides, SGS parameters reflect the degree of salivary gland involvement, severe patients with low parameters would have high histopathologic grades and biopsy focus scores.