Here are 2 links that could help you figure out what's best for your environnement; but I would really recommend using 2 NICs if your server will act as Proxy AND smtp relay, for security and performance.
Configuring an Inbound and Outbound SMTP Relay to Complement ISA 2004 Firewall Protection for Exchange Servers:
http://www.isaserver.org/articles/smtprelayinboundoutbound.htmlISA server 2004 - Single NIC config:
http://techrepublic.com.com/5208-11194-0.html?forumID=43&threadID=164933&messageID=1687121Hope this help
Eric