Objective To analyze the efficacy and safety of Intra-arterial chemotherapy (IAC) as secondly treatment in children with retinoblastoma (RB). Methods 42 eyes of 34 consecutive RB patients were enrolled in the study after intravenous chemotherapy (IVC), including 26 males and 8 females. The average age is 14.1 months. 21 cases were bilateral and 7 cases were unilateral. A total of 42 eyes of 34 patients were classified according to the International Intraocular Retinoblastoma Classification（IIRC）as group B(n=1, 2.4%), group C (n=3, 7.1%), group D (n=32, 76.2%), or group E (n=6, 14.3%). Tumor recurrence and tumor enlargement after IVC were 4 and 10 eyes respectively, accounting for 9.0% and 24.0% respectively. Sequential treatment after IVC followed by IAC were 28 eyes, accounting for 67.0%. All treatment eyes received IAC combined with laser, cryotherapy and other eye local treatment. The IAC regimen adopted the combination and alternation administration mode, by the combination of melphalan and carboplatin or the combination of melphalan and topotecan. According to the tumor changes after IAC decide whether IAC again. If tumors increased, vitreous or subretinal implants increased will be termination of IAC and enucleation. The mean follow-up time was (21.4±3.7) months after the last IAC treatment and (6.2±2.9) months after enucleation. Ocular preservation rate and complication were evaluated. Results The average IAC procedures performed on 42 eyes were (4.0±0.9). An overall ocular preservation rate of 76.2% was observed during follow-up periods due to calcification or inactivation of tumors (32 eyes), including group B (n=1, 100%), group C (n=1, 33.3%), group D (n=27, 84.4%), group E (n=3, 50%). 10 eyes were enucleated. Among them, 2 eyes of the tumor did not shrink after IAC, tumor recurrence (n=3), vitreous hemorrhage (n=3), enophthalmos (n=1), vitreous disseminated (n=1). 34 cases of children, transient eyelid oedema were 18 cases, vitreous hemorrhage and bone marrow suppression (Ⅰ-Ⅳ) were 1, 22 casese respectively. Conclusions IAC as secondly treatment is safe and effective for RB patients, however, there is still tumor recurrence. No serious ocular local and systemic complications were observed.